Fabrication of microscale medical devices by two-photon polymerization with multiple foci via a spatial light modulator

Two-photon polymerization is an appealing technique for producing microscale devices due to its flexibility in producing structures with a wide range of geometries as well as its compatibility with materials suitable for biomedical applications. The greatest limiting factor in widespread use of two-photon polymerization is the slow fabrication times associated with line-by-line, high-resolution structuring. In this study, a recently developed technology was used to produce microstructures by two-photon polymerization with multiple foci, which significantly reduces the production time. Computer generated hologram pattern technology was used to generate multiple laser beams in controlled positions from a single laser. These multiple beams were then used to simultaneously produce multiple microstructures by two-photon polymerization. Arrays of micro-Venus structures, tissue engineering scaffolds, and microneedle arrays were produced by multifocus two-photon polymerization. To our knowledge, this work is the first demonstration of multifocus two-photon polymerization technology for production of a functional medical device. Multibeam fabrication has the potential to greatly improve the efficiency of two-photon polymerization production of microscale devices such as tissue engineering scaffolds and microneedle arrays

Polyglycolic acid microneedles modified with inkjet-deposited antifungal coatings

In this study, the authors examined use of piezoelectric inkjet printing to apply an antifungal agent, voriconazole, to the surfaces of biodegradable polyglycolic acid microneedles. Polyglycolic acid microneedles with sharp tips (average tip radius = 25 ± 3 μm) were prepared using a combination of injection molding and drawing lithography. The elastic modulus (9.9 ± 0.3 GPa) and hardness (588.2 ± 33.8 MPa) values of the polyglycolic acid material were determined using nanoindentation and were found to be suitable for use in transdermal drug delivery devices. Voriconazole was deposited onto the polyglycolic acid microneedles by means of piezoelectric inkjet printing. It should be noted that voriconazole has poor solubility in water; however, it is readily soluble in many organic solvents. Optical imaging, scanning electron microscopy, energy dispersive x-ray spectrometry, and Fourier transform infrared spectroscopy were utilized to examine the microneedle geometries and inkjet-deposited surface coatings. F..

What is the Accretion Rate in NGC 4258?

We consider the implications of recent infrared and radio observations of the nucleus of NGC 4258. There is no direct evidence that the nucleus has been steadily accreting on the viscous timescale of the outer masing disk, which is >~ 10^9 \yr. Thus the mass accretion rate in the outer disk need not be the same as in the inner accretion flow where most of the gravitational binding energy is released. We show that an advection-dominated flow model with a transition radius of \sim (10-100) M (where M is the mass of the hole) and \mdot \approx 10^{-2}\msun \yr^{-1} is consistent with the observed spectrum from radio to X-rays. We also show that a thin (flat or warped) disk can fit the observed fluxes outside the X-ray band. The X-rays can be explained by means of a corona in such a model, but the absence of radio emission from the location of the putative central black hole provides a serious constraint on the properties of the corona. A wide range of accretion rates, 10^{-4} <~ \mdot <~ 10^{-2} \msun\yr^{-1}, can be made to fit the data, but the most ``natural'' models have 10^{-3} <~ \mdot <~ 10^{-2} \msun\yr^{-1}. Physical conditions in the observed VLBI jet features can also be related to conditions in the inner accretion flow. We conclude with a list of future observations that might help to constrain the accretion rate.Comment: 9 pages, 3 figures, latex, emulateapj.sty, submitted to Ap

MIP-based electrochemical protein profiling

We present the development of an electrochemical biosensor based on modified glassy carbon (GC) electrodes using hydrogel-based molecularly imprinted polymers (MIPs) has been fabricated for protein detection. The coupling of pattern recognition techniques via principal component analysis (PCA) has resulted in unique protein fingerprints for corresponding protein templates, allowing for MIP-based protein profiling. Polyacrylamide MIPs for memory imprinting of bovine haemoglobin (BHb), equine myoglobin (EMb), cytochrome C (Cyt C), and bovine serum albumin (BSA), alongside a non-imprinted polymer (NIP) control, were spectrophotometrically, and electrochemically characterised using modified GC electrodes. Rebinding capacities (Q) were revealed to be higher for larger proteins (BHb and BSA, Q ≈ 4.5) while (EMb and Cyt C, Q ≈ 2.5). Electrochemical results show that due to the selective nature of MIPs, protein arrival at the electrode via diffusion is delayed, in comparison to a NIP, by attractive selective interactions with exposed MIP cavities. However, at lower concentrations such discriminations are difficult due to low levels of MIP rebinding. PCA loading plots revealed 5 variables responsible for the separation of the proteins; Ep, Ip, E1/2 , Iat −0.8 V, �Idecay peak current to −0.8 V. Statistical symmetric measures of agreement using Cohen’s kappa coefficient (K) were revealed to be 63% for bare GC, 96% for NIP and 100% for MIP. Therefore, our results show that with the use of PCA such discriminations are achievable, also with the advantage of faster detection rates. The possibilities for this MIP technology once fully developed are vast, including uses in bio-sample clean-up or selective extraction, replacement of biological antibodies in immunoassays, as well as biosensors for medicine, food and the environment

Two-photon polymerization of microneedles for transdermal drug delivery

Microneedles are small-scale devices that are finding use for transdermal delivery of protein-based pharmacologic agents and nucleic acid-based pharmacologic agents; however, microneedles prepared using conventional microelectronics-based technologies have several shortcomings, which have limited translation of these devices into widespread clinical use

Pulsed Laser Deposition of Nanoporous Cobalt Thin Films

Nanoporous cobalt thin films were deposited on anodized aluminum oxide (AAO) membranes at room temperature using pulsed laser deposition. Scanning electron microscopy demonstrated that the nanoporous cobalt thin films retained the monodisperse pore size and high porosity of the anodized aluminum oxide substrates. Temperature- and field-dependent magnetic data obtained between 10 K and 350 K showed large hysteresis behavior in these materials. The increase of coercivity values was larger for nanoporous cobalt thin films than for multilayered cobalt/alumina thin films. The average diameter of the cobalt nanograins in the nanoporous cobalt thin films was estimated to be ~5 nm for blocking temperatures near room temperature. These results suggest that pulsed laser deposition may be used to fabricate nanoporous magnetic materials with unusual properties for biosensing, drug delivery, data storage, and other technological applications

Direct ink writing of polycaprolactone / polyethylene oxide based 3D constructs

There has been increasing interest over recent years in the application of three-dimensional (3D) printing technologies in the biomedical field. One such method is Direct Ink Writing (DIW); this approach has the potential advantage of allowing room-temperature deposition of materials, presented as an ink, to build complex architectures. DIW offers the ability to process biomaterials containing temperature-sensitive components. Due to the fabrication principles of DIW, there are specific rheological requirements that the ink must exhibit for the 3D construction. For this reason, hydrogel-based liquid feed stocks have been the focal point of ink development. As a consequence, studies based on inks comprising hydrophobic biomaterials, which are insoluble in water and hence unsuited to the hydrogel approach, have been limited. In this study, we investigate novel inks that utilize polycaprolactone (PCL), a hydrophobic polymer, as the primary constituent by dissolving the polymer in solvent systems based on dichloromethane (DCM) and acetone (ACE). Moreover, polyethylene oxide (PEO) was incorporated into the PCL systems in order to extend the range of hydrophilicity of the systems. The rheological properties of the inks were investigated as a function of polymer composition and solvent system. Woodpile constructs of PCL and PCL/PEO were fabricated using DIW method and were assessed by a series of material characterisation. The type of solvent system had a noticeable impact on the ink rheology, which ultimately affected the surface properties. The incorporation of PEO particularly enhanced the roughness and wettability of the constructs. Our results support the use of DIW as a new means to process hydrophobic polymers for biomedical applications

Nanoporous membranes for medical and biological applications

Synthetic nanoporous materials have numerous potential biological and medical applications that involve sorting, sensing, isolating and releasing biological molecules. Nanoporous systems engineered to mimic natural filtration systems are actively being developed for use in smart implantable drug delivery systems, bioartificial organs, and other novel nano-enabled medical devices. Recent advances in nanoscience have made it possible to precisely control the morphology as well as physical and chemical properties of the pores in nanoporous materials that make them increasingly attractive for regulating and sensing transport at the molecular level. In this work, an overview of nanoporous membranes for biomedical applications is given. Various in vivo and in vitro membrane applications, including biosensing, biosorting, immunoisolation and drug delivery, are presented. Different types of nanoporous materials and their fabrication techniques are discussed with an emphasis on membranes with ordered pores. Desirable properties of membranes used in implantable devices, including biocompatibility and antibiofouling behavior, are discussed. The use of surface modification techniques to improve the function of nanoporous membranes is reviewed. Despite the extensive research carried out in fabrication, characterization, and modeling of nanoporous materials, there are still several challenges that must be overcome in order to create synthetic nanoporous systems that behave similarly to their biological counterparts

Biochemical Properties of Tissue-Engineered Cartilage

Microtia is treated with rib cartilage sculpting and staged procedures; though aesthetically pleasing, these constructs lack native ear flexibility. Tissue-engineered (TE) elastic cartilage may bridge this gap; however, TE cartilage implants lead to hypertrophic changes with calcification and loss of flexibility. Retaining flexibility in TE cartilage must focus on increased elastin, maintained collagen II, decreased collagen X, with prevention of calcification. This study compares biochemical properties of human cartilage to TE cartilage from umbilical cord mesenchymal stem cells (UCMSCs). Our goal is to establish a baseline for clinically useful TE cartilage